Dataset Information

The cortical signature of prodromal AD: regional thinning predicts mild AD dementia.

ABSTRACT:

Objective

We previously used exploratory analyses across the entire cortex to determine that mild Alzheimer disease (AD) is reliably associated with a cortical signature of thinning in specific limbic and association regions. Here we investigated whether the cortical signature of AD-related thinning is present in individuals with questionable AD dementia (QAD) and whether a greater degree of regional cortical thinning predicts mild AD dementia.

Methods

Participants included 49 older adults with mild impairment consistent with mild cognitive impairment (Clinical Dementia Rating [CDR] = 0.5) at the time of structural MRI scanning. Cortical thickness was measured in nine regions of interest (ROIs) identified previously from a comparison of patients with mild AD and controls.

Results

Longitudinal clinical follow-up revealed that 20 participants converted to mild AD dementia (progressors) while 29 remained stable (nonprogressors) approximately 2.5 years after scanning. At baseline, QAD participants showed a milder degree of cortical thinning than typically seen in mild AD, and CDR Sum-of-Boxes correlated with thickness in temporal and parietal ROIs. Compared to nonprogressors, progressors showed temporal and parietal thinning. Using receiver operating characteristic curves, the thickness of an aggregate measure of these regions predicted progression to mild AD with 83% sensitivity and 65% specificity.

Conclusions

Thinning in specific cortical areas known to be affected by Alzheimer disease (AD) is detectable in individuals with questionable AD dementia (QAD) and predicts conversion to mild AD dementia. This method could be useful for identifying individuals at relatively high risk for imminent progression from QAD to mild AD dementia, which may be of value in clinical trials.

SUBMITTER: Bakkour A

PROVIDER: S-EPMC2677470 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Publications

The cortical signature of prodromal AD: regional thinning predicts mild AD dementia.

Bakkour Akram A Morris John C JC Dickerson Bradford C BC

Neurology 20081224 12

<h4>Objective</h4>We previously used exploratory analyses across the entire cortex to determine that mild Alzheimer disease (AD) is reliably associated with a cortical signature of thinning in specific limbic and association regions. Here we investigated whether the cortical signature of AD-related thinning is present in individuals with questionable AD dementia (QAD) and whether a greater degree of regional cortical thinning predicts mild AD dementia.<h4>Methods</h4>Participants included 49 old ...[more]

PMID: 19109536

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Project description:INTRODUCTION:The diagnosis of mild cognitive impairment (MCI) refers to cognitive impairment not meeting dementia criteria. A survey among members of the American Association of Neurology (AAN) showed that MCI was considered a useful diagnosis. Recently, research criteria have been proposed for the diagnosis of Alzheimer's disease (AD) in MCI based on AD biomarkers (prodromal AD/MCI due to AD). The aim of this study was to investigate the attitudes of clinicians in Europe on the clinical utility of MCI and prodromal AD/MCI due to AD criteria. We also investigated whether the prodromal AD/MCI due to AD criteria impacted management of MCI patients. METHODS:An online survey was performed in 2015 among 102 members of the European Academy of Neurology (EAN) and the European Alzheimer's Disease Consortium (EADC). Questions were asked on how often criteria were used, how they were operationalized, how they changed patient management, and what were considered advantages and limitations of MCI and prodromal AD/MCI due to AD. The questionnaire consisted of 47 questions scored on a Likert scale. RESULTS:Almost all respondents (92%) used the MCI diagnosis in clinical practice. Over 80% of the EAN/EADC respondents found a MCI diagnosis useful because it helped to label the cognitive problem, involve patients in planning for the future, and start risk reduction activities. These findings were similar to those reported in the AAN survey. Research criteria for prodromal AD/MCI due to AD were used by 68% of the EAN/EADC respondents. The most common reasons to use the criteria were increased certainty of diagnosis (86%), increased possibilities to provide counseling (51%), facilitation of follow-up planning (48%), start of medical intervention (49%), and response to patients' wish for a diagnosis (41%). Over 70% of the physicians considered that a diagnosis of prodromal AD/MCI due to AD had an added value over the MCI diagnosis. CONCLUSIONS:The diagnostic criteria of MCI and prodromal AD/MCI due to AD are commonly used among EAN/EADC members. The prodromal AD/MCI due to AD were considered clinically useful and impacted patient management and communication.

Project description:In the military, explosive blasts are a significant cause of mild traumatic brain injuries (mTBIs). The symptoms associated with blast mTBIs causes significant economic burdens and a diminished quality of life for many service members. At present, the distinction of the injury mechanism (blast versus non-blast) may not influence TBI diagnosis. However, using noninvasive imaging, this study reveals significant distinctions between the blast and non-blast TBI mechanisms. A cortical whole-brain thickness analysis was performed using structural high-resolution T1-weighted MRI to identify the effects of blasts in persistent mTBI (pmTBI) subjects. A total of 41 blast pmTBI subjects were individually age- and gender-matched to 41 non-blast pmTBI subjects. Using FreeSurfer, cortical thickness was quantified for the blast group, relative to the non-blast group. Cortical thinning was identified within the blast mTBI group, in two clusters bilaterally. In the left hemisphere, the cluster overlapped with the lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, superior frontal, rostral anterior cingulate and frontal pole cortices (p < 0.02, two-tailed, size = 1680 mm2). In the right hemisphere, the cluster overlapped with the lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, pars orbitalis, pars triangularis and insula cortices (p < 0.002, two-tailed, cluster size = 2453 mm2). Self-report assessments suggest significant differences in the Post-Traumatic Stress Disorder Checklist-Civilian Version (p < 0.05, Bonferroni-corrected) and the Neurobehavioral Symptom Inventory (p < 0.01, uncorrected) between the blast and non-blast mTBI groups. These results suggest that blast may cause a unique injury pattern related to a reduction in cortical thickness within specific brain regions which could affect symptoms. No other study has found cortical thickness difference between blast and non-blast mTBI groups and further replication is needed to confirm these initial observations.

Dataset Information

The cortical signature of prodromal AD: regional thinning predicts mild AD dementia.

Objective

Methods

Results

Conclusions

Publications

The cortical signature of prodromal AD: regional thinning predicts mild AD dementia.

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